Objective To explore the correlation of MET status in patients with advanced prostatic acinar adenocarcinoma with the clinical pathological parameters and prognosis. Methods The specimen from 135 patients with advanced prostatic acinar adenocarcinoma was included. The expression of c-MET protein was detected via immunohistochemistry, and MET gene amplification was assessed by fluorescence in situ hybridization. The relationships of c-MET expression and gene amplification with clinicopathological features and prognosis were analyzed. Results The positive expression rate of c-MET was 52.60% (71/135). Compared with the c-MET expression in adjacent tissues, that in tumor tissues showed lower heterogeneous expression. Among the cases, 1.71% (2/117) exhibited MET gene polyploidy, but no gene amplification was detected. Positive c-MET expression was significantly correlated with high Gleason scores and grade groups (P=0.0073). However, no significant relationship was found between c-MET expression and progression-free survival or post-treatment t-PSA levels. Conclusion c-MET protein is expressed at a relatively low level in advanced prostatic acinar adenocarcinoma, suggesting that c-MET may not be a viable target for ADC drug development in prostatic acinar adenocarcinoma.

Objective To observe the value of intraoperative ultrasound(IOUS)for microsurgical resection of primary supratentorial glioblastoma.Methods Totally 130 cases of central nervous system WHO grade 4 primary supratentorial glioblastoma confirmed by postoperative pathology were retrospectively enrolled and divided into IOUS group and control group(each n=65)based on whether IOUS was used during operation.The general information,resection related indicators and postoperative complications were compared between groups,and the application value of IOUS was analyzed.Results In IOUS group,the tumor depth was greater,while the intraoperative bleeding,duration of hospitalization and operation-duration were all less than those in control group(all P＜0.05).Postoperative complications occurred in 28 cases of IOUS group and 29 cases of control group,and the incidence of subdural effusion in IOUS group was lower than that in control group(P＜0.05).Conclusion IOUS could effectively reduce intraoperative bleeding,duration of hospitalization,operation-duration and incidence of postoperative subdural effusion in microsurgical resection of primary supratentorial glioblastoma.

Objective To investigate the value of intraoperative ultrasound radiomics for predicting isocitrate dehydrogenase 1(IDH1)mutation of high-grade glioma.Methods Ninety-five patients with high-grade glioma(WHO grade Ⅲ and Ⅳ)who underwent craniotomy glioma resection and ultrasound assisted tumor localization during operation and then confirmed by pathology were retrospectively enrolled.The patients were divided into training set(n=66,including 24 IDH1 mutation type and 42 IDH1 wild type)and validation set(n=29,including 11 IDH1 mutation type and 18 IDH1 wild type)at the ratio of 7∶3.Based on intraoperative ultrasound,radiomics features were extracted,the best ones were screened,and a radiomics model was established for predicting IDH1 mutation of high-grade glioma using random forest algorithm.Receiver operating characteristic(ROC)curve was plotted,the area under the curve(AUC)was calculated to evaluate the predictive efficacy of the model,and decision curve analysis(DCA)was used to evaluate the clinical value of the model.Results A total of 851 radiomics features were extracted based on intraoperative ultrasound,and finally 5 best ones were screened out to construct a radiomics model.The AUC of the radiomics model for predicting IDH1 mutation of high-grade glioma in training and validation sets was 0.902 and 0.707,respectively,with no significant difference(P=0.097).DCA maps showed that the clinical net benefit of the radiomics model was high.Conclusion Intraoperative ultrasound radiomics could effectively predict IDH1 mutation of high-grade glioma.

BACKGROUND:There are some problems such as bone fusion failure or peri-implant infection after implantation of pure titanium implants.Therefore,surface improvement of titanium implants has become a hot topic in research.Macrophages are an immune defense line of the body in response to external stimuli,and the relevant immune response of any biomaterials implanted in the body is related to macrophages. OBJECTIVE:The graphene oxide/hydroxyapatite composite coating on titanium alloy surface was prepared by electrochemical deposition method.The surface characteristics of the coating and the growth and polarization of macrophage RAW264.7 on the surface were analyzed. METHODS:The graphene oxide coating and graphene oxide/hydroxyapatite composite coating on titanium alloy surface was prepared by electrochemical deposition method.The physical properties of the coating were characterized.Pure titanium sheets(blank group),titanium sheets deposited with pure GO coating(control group)and titanium sheets deposited with graphene oxide/hydroxyapatite composite coating(experimental group)were co-cultured with macrophages RAW264.7,respectively.Cell proliferation was detected by CCK-8 assay and DAPI staining.Cell adhesion on the surface of titanium was observed by scanning electron microscopy,and cell polarization phenotype was detected by flow cytometry. RESULTS AND CONCLUSION:(1)Under scanning electron microscope,the pure titanium sheet showed directional scratches and a few punctate pits.After the pure graphene oxide coating was deposited,the surface of titanium sheet showed more cracks,gullies and particles of uneven size,and the wrinkle-like structure characterized by graphene oxide.After the composite coating was deposited,the surface of the titanium sheet was smooth,and the pellet size was more uniform.The water contact angle of composite coated titanium sheet was lower than that of pure titanium sheet and pure graphene oxide coated titanium sheet(P<0.05).(2)CCK-8 assay and DAPI staining showed that compared with the blank group and the control group,the cell proliferation in the experimental group was faster.Scanning electron microscopy showed that RAW264.7 cells all adhered to the surface of the three groups of titanium sheets.With the extension of culture time,cell morphology changed from round to spindle shape.After 7 days of culture,cells in the blank group extended short and few pseudopods;cells in the control group extended long and more pseudopods,and cells in the experimental group extended short and more pseudopods,and the overall cell fullness in the experimental group was the best.Flow cytometry results showed that the cells in the experimental group showed a higher proportion of M2 polarization in the anti-inflammatory direction.(3)These findings conclude that graphene oxide/hydroxyapatite composite coating has good physical,chemical,and biological properties.

BACKGROUND:Titanium and titanium-coated materials are widely used in the field of oral implantology,but there are still phenomena such as peri-implantitis,implant loss and loosening.Therefore,the surface modification of pure titanium has become a hot topic in oral medicine research. OBJECTIVE:To investigate the physical and osteogenic properties of hydroxyapatite-graphene oxide composite coating on titanium surface. METHODS:Hydroxyapatite-graphene oxide composite coatings were prepared on the titanium surface by electrodeposition at voltages of 10,30,and 50 V.The micromorphology and hydrophilic properties of the coatings were characterized,and the composite coatings prepared under the optimal voltage conditions were screened for animal experiments.Fifty-four SD rats were selected to prepare defects of 2 mm in diameter and 7 mm in depth on the femoral head of both hind limbs,and were randomly divided into 3 groups with 18 rats in each group:no titanium material was implanted in the blank group;pure titanium material was implanted in the pure titanium group,and coated titanium material loaded with hydroxyapatite-graphene oxide composite coating was implanted in the coated group.The osteogenesis effect was observed by X-ray,Micro-CT scan,and pathological section staining at 4,8,and 12 weeks after implantation. RESULTS AND CONCLUSION:(1)Under scanning electron microscopy,when the voltage was 10 V,there were a lot of cracks and clumps in the coating.When the voltage rose to 30 V,there were still some small clumps in the coating,but the overall uniformity was relatively flat.When the voltage was 50 V,the coating was more evenly distributed and cracks and spots were reduced.The hydrophilicity of the composite coating prepared at 50 V voltage was the best.In summary,the composite coating material prepared at 50 V voltage was selected in animal experiments.(2)The X-ray film showed that the implant position was relatively fixed,and no serious postoperative inflammation occurred.The results of Micro-CT scan showed that the new bone formation rate and bone formation volume on the implant surface of the coated group were better than those of the pure titanium group(P<0.001).The results of Micro-CT scan were further confirmed by hematoxylin-eosin staining and Masson staining in pathological sections.Immunohistochemical staining of pathological sections showed that the expressions of osteopontin and bone morphogenetic protein 2 in the pure titanium group were higher than those in the blank group at week 12 after implantation(P<0.001),and those in the coated group were higher than those in the pure titanium group at week 12 after implantation(P<0.001).(3)The results show that the hydroxyapatite-graphene oxide composite coating material has good physical and osteogenic properties.

BACKGROUND:The regulation of M1/M2 polarization direction of macrophages is particularly critical in tissue engineering applications,and timely regulation can minimize proinflammatory,anti-inflammatory,or tissue healing responses. OBJECTIVE:To implant lentivirus-mediated miRNA-378a macrophage strain complex collagen to detect the expression level of immune regulation in the in vivo environment,and further clarify the influence of miRNA-378a in promoting macrophage M2 polarization in immune regulation and tissue repair in the in vivo environment. METHODS:Lentivirus-mediated miRNA-378a overexpressing macrophage cell lines and negative control virus macrophage lines were amplified and screened,and the macrophage lines were recovered and cultured together with collagen sponge to form a composite scaffold,which was divided into the following groups:(1)Positive group:miRNA-378a overexpressing macrophage-collagen sponge composite;(2)negative group:negative control of virus-mediated miRNA-378a macrophage-collagen sponge composite;(3)control group:macrophage-collagen sponge;(4)blank control group:collagen sponge.The cell density,phenotype,and adhesion of each group were observed by immunofluorescence and scanning electron microscopy.The cells were implanted into the subcutaneous model of the back of mice,and the mice were sacrificed 4 and 7 days after modeling.The direction of macrophage polarization in the collagen sponge composite of macrophages with miRNA-378a overexpression mediated by lentivirus and its effect on immune regulation and tissue repair were analyzed by gross observation,hematoxylin-eosin staining,MASSON staining,and immunohistochemistry. RESULTS AND CONCLUSION:(1)Under immunofluorescence microscopy,the macrophage cell lines in each group were observed to form a composite scaffold with the collagen sponge.(2)Under scanning electron microscope,lentivirus-mediated miRNA-378a macrophages in the positive group proliferated in cell density,had spherical,elliptic and polygonal differentiation,and had more pseudofeet than other groups.(3)Under general observation,the overall 7-day healing was better than that at 4 days.Lentivirus-mediated miRNA-378a macrophages in the positive group healed better than other groups regardless of 4 and 7 days.(4)Lentivirus-mediated miRNA-378a macrophages in the positive group under hematoxylin-eosin staining and MASSON staining had more amounts of fibrocytes,capillaries,fibroblasts,and collagen fiber hyperplasia.(5)Immunohistochemistry showed that lentivirus-mediated miRNA-378a macrophages in the positive group were more positive in 4-and 7-day M2 polarized cells than in other groups.The macrophages of the control and negative groups in 4-and 7-day M2 polarized cells were greater than that of the blank control group.There was no statistical difference between the control group and the negative group.The number of stained cells in the positive,negative,and control groups regardless of 4 and 7 days was higher than that in the blank control group,and the positive group>negative group ≈ control group>blank control group.(6)It is concluded that macrophages with miRNA-378a overexpression have a large amount of fibroblasts,capillaries,fibroblasts,and collagen fiber hyperplasia in vivo,which has a positive effect on tissue repair,and can promote the polarization of macrophages towards M2 type and inhibit the polarization of M1 type,thus contributing to reducing the inflammatory response of the body.

Objective : To investigate whole genome information of a newly isolatedBifidobacterium animalissubsp. lactic B4 strain from healthy human feces was analyzed and its probiotic properties. Methods : The antimicrobial resistance, hemolytic, gastric acid tolerance and biochemical characteristics of B. animalis B4 were evaluated byin vitroexperiments, and its whole genome was sequentially sequenced and functional annotation was performed by next and three-generation sequencing technology. Results: Whole genome sequencing of B. animalis B4 showed that its genome size was 1 944 146 bp, with GC content of 60.49%, no plasmid, and a total of 1 642 genes. The results ofin vitroanalysis showed that the B. animalis B4 had good probiotic properties, including non-hemolytic and stomach acid resistance. At the same time, the genome results showed that the B. animalis B4 strain did not have toxin and disease-related genes, drug resistance genes were few and the transmission ability was not high, so it had high safety. Gene annotation of KEGG, COG and GO showed that it contained many biological active enzymes, such as β-galactosidase, L-lactate dehydrogenase and other probiotic genes. Conclusion The B. animalis B4 has good probiotic properties, showing excellent safety at the genetic level, with a probiotic gene sequence.

Objective To investigate the relationship between biological aging and the rate of cognitive decline in middle-aged and elderly populations.Methods Longitudinal tracking data of cognitive function were obtained from the China Health and Retirement Longitudinal Study(CHARLS).We employed the Klemera and Doubal method(KDM)to estimate biological age(BA),and calculate the biological aging index(BAI)and biological aging type(BAT).A multivariate linear regression model was employed to analyze the relationships between baseline BAI,BAT,and cognitive function scores.Based on the baseline analysis,a mixed-effects model was used to examine the longitudinal associations between baseline BAI,BAT,and cognitive function during follow-up.Results A total of 5 897 participants were included in the study.BAI was found to be negatively associated with baseline cognitive function scores,with the partial regression coefficient(β)(95％CI)being-0.185(—0.231,—0.139)(P＜0.001).Compared with the lagged aging group,the premature aging group had lower cognitive function scores(β[95％CI]:—0.741[—0.966,—0.516]).For age and sex,for each additional year of baseline BAI,cognitive function scores declined by an average of 0.012(95％CI:—0.019,—0.005)points per year after adjusting for age and sex,and declined by 0.011(95％CI:—0.018,—0.004)points per year after adjusting for other covariates.Compared with participants with lagged aging,those with premature aging experienced,on average,an additional decline of 0.042(95％CI:—0.075,0.009)points per year in cognitive function scores after adjusting for age and sex alone,and by 0.039(95％CI:—0.072,—0.007)points per year after adjusting for other covariates.Conclusion Biological aging affects the rate of cognitive decline in middle-aged and elderly populations.A higher BAI is associated with a faster decline in cognitive function.Compared with those with lagged aging,individuals with premature aging exhibit a more rapid rate of cognitive decline.

Objective To observe the value of intraoperative ultrasound(IOUS)for microsurgical resection of primary supratentorial glioblastoma.Methods Totally 130 cases of central nervous system WHO grade 4 primary supratentorial glioblastoma confirmed by postoperative pathology were retrospectively enrolled and divided into IOUS group and control group(each n=65)based on whether IOUS was used during operation.The general information,resection related indicators and postoperative complications were compared between groups,and the application value of IOUS was analyzed.Results In IOUS group,the tumor depth was greater,while the intraoperative bleeding,duration of hospitalization and operation-duration were all less than those in control group(all P＜0.05).Postoperative complications occurred in 28 cases of IOUS group and 29 cases of control group,and the incidence of subdural effusion in IOUS group was lower than that in control group(P＜0.05).Conclusion IOUS could effectively reduce intraoperative bleeding,duration of hospitalization,operation-duration and incidence of postoperative subdural effusion in microsurgical resection of primary supratentorial glioblastoma.

Objective To investigate the value of intraoperative ultrasound radiomics for predicting isocitrate dehydrogenase 1(IDH1)mutation of high-grade glioma.Methods Ninety-five patients with high-grade glioma(WHO grade Ⅲ and Ⅳ)who underwent craniotomy glioma resection and ultrasound assisted tumor localization during operation and then confirmed by pathology were retrospectively enrolled.The patients were divided into training set(n=66,including 24 IDH1 mutation type and 42 IDH1 wild type)and validation set(n=29,including 11 IDH1 mutation type and 18 IDH1 wild type)at the ratio of 7∶3.Based on intraoperative ultrasound,radiomics features were extracted,the best ones were screened,and a radiomics model was established for predicting IDH1 mutation of high-grade glioma using random forest algorithm.Receiver operating characteristic(ROC)curve was plotted,the area under the curve(AUC)was calculated to evaluate the predictive efficacy of the model,and decision curve analysis(DCA)was used to evaluate the clinical value of the model.Results A total of 851 radiomics features were extracted based on intraoperative ultrasound,and finally 5 best ones were screened out to construct a radiomics model.The AUC of the radiomics model for predicting IDH1 mutation of high-grade glioma in training and validation sets was 0.902 and 0.707,respectively,with no significant difference(P=0.097).DCA maps showed that the clinical net benefit of the radiomics model was high.Conclusion Intraoperative ultrasound radiomics could effectively predict IDH1 mutation of high-grade glioma.